We plan to assess several areas of importance to the field of alcoholism and its effects: 1) Sedatives in Health and Liver Disease. Initially we will determine the possible effects of smoking, sex and birth control pills on the elimination of Librium in normal man. Subsequent studies will be carried out to determine how the presence of alcoholic liver disease affects the metabolism of Librium and Valium when these drugs are given over a prolonged time. None of this information is currently available. The studies will be carried out using conventional pharmacokinetic analyses and laboratory assays now available in our unit. Other studies on sedatives will evaluate the sensitivity of the brain in the aged, patients with alcoholic liver disease, those smoking and those who are alcoholics without liver disease to Librium, Valium, and Ativan (lorazepam). This assessment of drug pharmacodynamics will utilize computerized psychometric performance and EEG patterns. 2) Thiamine Metabolism. We will continue our studies of a) thiamine transport via the liver and the effects of alcohol on this, b) attempts to detect and characterize a thiamine-binding protein in gut mucosa, c) phosphorylation of thiamine in gut wall, and d) the absorption rate of thiamine by gut of rats deficient in other vitamins. The techniques will consist of isolated rat hepatocytes or gut sacs incubated with varying concentrations of 35S-thiamine. The phosphorylated thiamines will be separated by electrophoresis and binding protein searched for by equilibrium dialysis and affinity chromatography. 3) Vitamin B6 Metabolism. We will continue to search for the sites (organs) wherein pyridoxal-5'-phosphate is metabolized in vivo. Organs to be assessed are muscle, lung and bone, since liver, kidney, gut, spleen and erythrocytes have been ruled out. We also hope (with Drs. Li and Lumeng) to prepare pure 14C-PLP and assess the effect of alcoholic liver disease on plasma protein binding of labeled PLP. 4) Fetal Alcohol Syndrome. We plan to continue our studies on the transport of amino acids via the placenta exposed to alcohol for short and prolonged periods of time.